ArticleInternational journal of molecular sciences2019
Mechanisms of PKC-Mediated Enhancement of HIF-1α Activity and its Inhibition by Vitamin K2 in Hepatocellular Carcinoma Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Protein Kinase C-Delta (PKCδ) inhibition stabilizes endothelium and suppresses triple-negative breast cancer (TNBC) intravasation in a microfluidic hypoxic tumor model.Bioengineering & translational medicine · 2026Article
- Differential Role of CD318 in Tumor Immunity Affecting Prognosis in Colorectal Cancer Compared to Other Adenocarcinomas.Journal of clinical medicine · 2025Article
- Reducing PKCδ inhibits tumor growth through growth hormone by inhibiting PKA/CREB/ERK signaling pathway in pituitary adenoma.Scientific reports · 2025Article
- Hypoxia Modulates Transmembrane Prostatic Acid Phosphatase (TM-PAP) in MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Growth factor and hypoxia-inducible factor alpha content in the retina of male Wistar rats in experimental diabetic retinopathy and the effect of cellular protein kinase blockade.Frontiers in endocrinology · 2025Article
- Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.International journal of molecular sciences · 2024Article
- The biological responses of vitamin K2: A comprehensive review.Food science & nutrition · 2023Review
- A comprehensive computational analysis to explore the importance of SIGLECs in HCC biology.BMC gastroenterology · 2023Article
- Review
- VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway.European journal of histochemistry : EJH · 2022Article
- Bladder cancer cell lines adapt their aggressiveness profile to oxygen tension.Oncology letters · 2022Article
- S1P Stimulates Erythropoietin Production in Mouse Renal Interstitial Fibroblasts by S1PInternational journal of molecular sciences · 2021Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Vitamin K and hepatocellular carcinoma: The basic and clinic.World journal of clinical cases · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) plays important roles in cancer cell biology. HIF-1α is reportedly activated by several factors, including protein kinase C (PKC), in addition to hypoxia. We investigated the role of PKC isoforms and the effects of vitamin K2 (VK2) in the activation process of HIF-1α. Human hepatocellular carcinoma (HCC)-derived Huh7 cells were cultured under normoxic and hypoxic (1% O₂) conditions with or without the PKC stimulator TPA. The expression, transcriptional activity and nuclear translocation of HIF-1α were examined under treatment with PKC inhibitors, siRNAs against each PKC isoform and VK2. Hypoxia increased the expression and activity of HIF-1α. TPA increased the HIF-1α activity several times under both normoxic and hypoxic conditions. PKC-δ siRNA-mediated knockdown, PKC-δ inhibitor (rottlerin) and pan-PKC inhibitor (Ro-31-8425) suppressed the expression and transcriptional activity of HIF-1α. VK2 significantly inhibited the TPA-induced HIF-1α transcriptional activity and suppressed the expression and nuclear translocation of HIF-1α induced by TPA without altering the HIF-1α mRNA levels. These data indicate that PKC-δ enhances the HIF-1α transcriptional activity by increasing the nuclear translocation, and that VK2 might suppress the HIF-1α activation through the inhibition of PKC in HCC cells.
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